What are the diagnostic and treatment approaches for a patient suspected of having Amyotrophic Lateral Sclerosis (ALS)?

Diagnostic and Treatment Approaches for Amyotrophic Lateral Sclerosis (ALS)

The diagnosis of ALS requires evidence of both upper and lower motor neuron degeneration, progressive spread of symptoms, and exclusion of other conditions through a combination of clinical evaluation, electrophysiological studies, and neuroimaging. 1, 2

Diagnostic Approach

Clinical Evaluation

• ALS presents with mixed upper motor neuron signs (hypertonicity, hyperreflexia) and lower motor neuron signs (fasciculations, weakness, atrophy) 2
• Approximately 80% of patients with bulbar-onset ALS develop dysarthria and dysphagia 2
• Mean time from symptom onset to diagnosis is typically around 12 months, but earlier diagnosis is associated with better outcomes 3

Essential Diagnostic Tests

• Electromyography (EMG) and nerve conduction velocity (NCV) studies are cornerstone tests for diagnosing ALS, detecting lower motor neuron degeneration and distinguishing ALS from other conditions 1
• MRI of the brain without IV contrast is recommended for initial imaging to exclude other conditions 4, 1
  • Common findings include abnormal T2/FLAIR signal in the corticospinal tracts, particularly in the posterior limb of the internal capsule and cerebral peduncles 4
  • T2*-weighted or susceptibility-weighted imaging may show abnormal hypointensity in the precentral gyrus and gray matter, which can be highly sensitive and specific for ALS 4, 1
• MRI of the spine without IV contrast may be appropriate in certain cases to exclude structural, infectious, or neoplastic etiologies 4, 1

Laboratory Tests to Exclude Mimics

• Complete blood count (CBC) to evaluate for infectious or inflammatory conditions 1
• Blood chemistry profile including glucose, electrolytes, kidney function, and liver enzymes 1
• Thyroid function tests to rule out thyroid disorders that can cause weakness 1
• Vitamin B12, folate, and vitamin E levels to exclude deficiencies 1
• Serum protein electrophoresis to rule out paraproteinemic neuropathies 1
• Anti-ganglioside antibodies to exclude immune-mediated motor neuropathies 1
• Paraneoplastic antibody panel to exclude paraneoplastic syndromes 1
• Anti-acetylcholine receptor and anti-MuSK antibodies to rule out myasthenia gravis 1

Cerebrospinal Fluid (CSF) Examination

• CSF analysis including cell count, protein, glucose, IgG index, oligoclonal bands, and cytology to exclude infectious, inflammatory, or neoplastic causes 1
• CSF protein may be normal or mildly elevated in ALS, but marked pleocytosis suggests alternative diagnoses 1

Genetic Testing

• Consider genetic testing for ALS-associated genes (e.g., C9orf72, SOD1, FUS, TARDBP), especially in cases with family history 1, 5
• Approximately 10% of ALS cases have a family history suggesting autosomal dominant inheritance 6

Swallowing Evaluation in ALS

• Structured questionnaires (e.g., EAT-10) can help identify patients with unsafe airway protection during swallowing (sensitivity 86%, specificity 76%) 4
• Volume-Viscosity Swallow Test (V-VST) has high sensitivity (92%) and specificity (80%) for detecting dysphagia in ALS patients 4
• Videofluoroscopy is recommended in the clinical evaluation of dysphagia at diagnosis 4
  • Can detect early signs of dysphagia even in patients without bulbar symptoms 4
  • Common findings include oral stasis, piecemeal swallowing, and decreased pharyngo-esophageal motility 4

Treatment Approach

FDA-Approved Medications

• Riluzole (50 mg twice daily) is indicated for the treatment of ALS 7
  • Extends survival by approximately 60-90 days compared to placebo 7
  • Should be taken at least 1 hour before or 2 hours after meals 7
  • Requires monitoring of serum aminotransferases before and during treatment 7
  • Early initiation of therapy may slow the neurodegenerative process 3

Supportive Care

• Nutritional support is essential for patients with dysphagia and weight loss 2
• Regular swallowing evaluations (recommended every 3 months) to monitor dysphagia progression 4
• Early referral to palliative services is recommended to establish relationships with staff and address end-of-life issues before communication becomes limited 2

Prognosis

• Mean survival of typical ALS patients is 3-5 years after symptom onset 2
• Only 5-10% of patients live longer than 10 years 2
• Respiratory failure due to respiratory muscle weakness is the most common cause of death 2

Important Considerations

• Early diagnosis and treatment initiation are associated with better outcomes and reduced psychological distress 3
• Multidisciplinary care results in cost savings and prolonged survival 3
• Support for caregivers is crucial, as they often experience significant burden 2